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The concept of race is prevalent in medical, nursing, and public health literature. Clinicians often incorporate race into diagnostics, prognostic tools, and treatment guidelines. An example is the recently heavily debated use of race and ethnicity in the Vaginal Birth After Cesarean (VBAC) calculator. In this case, the critics argued that the use of race in this calculator implied that race confers immutable characteristics that affect the ability of women to give birth vaginally after a c-section. This debate is co-occurring as research continues to highlight the racial disparities in health outcomes, such as high maternal mortality among Black women compared to other racial groups in the United States. As the healthcare system contemplates the necessity of utilizing race-a social and political construct, to monitor health outcomes, it has sparked more questions about incorporating race into clinical algorithms, including pulmonary tests, kidney function tests, pharmacotherapies, and genetic testing. This paper critically examines the argument against the race-based Vaginal Birth After Cesarean (VBAC) calculator, shedding light on its implications. Moreover, it delves into the detrimental effects of normalizing race as a biological variable, which hinders progress in improving health outcomes and equity.

Exploring the relationship between neuronal dynamics and ethologically relevant behaviour involves recording neuronal-population activity using technologies that are compatible with unrestricted animal behaviour. However, head-mounted microscopes that accommodate weight limits to allow for free animal behaviour typically compromise field of view, resolution or depth range, and are susceptible to movement-induced artefacts. Here we report a miniaturized head-mounted fluorescent mesoscope that we systematically optimized for calcium imaging at single-neuron resolution, for increased fields of view and depth of field, and for robustness against motion-generated artefacts. Weighing less than 2.5 g, the mesoscope enabled recordings of neuronal-population activity at up to 16 Hz, with 4 mu m resolution over 300 mu m depth-of-field across a field of view of 3.6 x 3.6 mm2 in the cortex of freely moving mice. We used the mesoscope to record large-scale neuronal-population activity in socially interacting mice during free exploration and during fear-conditioning experiments, and to investigate neurovascular coupling across multiple cortical regions. An optimized head-mounted fluorescent mesoscope enables large-scale calcium imaging at single-neuron resolution in freely moving mice, facilitating neurobehavioural studies during social interactions and fear-conditioning experiments.

Optical projection tomography (OPT) is a three-dimensional mesoscopic imaging modality that can use absorption or fluorescence contrast, and is widely applied to fixed and live samples in the mm-cm scale. For fluorescence OPT, we present OPT implemented for accessibility and low cost, an open-source research-grade implementation of modular OPT hardware and software that has been designed to be widely accessible by using low-cost components, including light-emitting diode (LED) excitation and cooled complementary metal-oxide-semiconductor (CMOS) cameras. Both the hardware and software are modular and flexible in their implementation, enabling rapid switching between sample size scales and supporting compressive sensing to reconstruct images from undersampled sparse OPT data, e.g. to facilitate rapid imaging with low photobleaching/phototoxicity. We also explore a simple implementation of focal scanning OPT to achieve higher resolution, which entails the use of a fan-beam geometry reconstruction method to account for variation in magnification. This article is part of the Theo Murphy meeting issue 'Open, reproducible hardware for microscopy'.

JGP study shows that hydrophobic residues in the S1 transmembrane domain modulate the voltage-sensor movements and enzymatic activity of voltage-sensing phosphatase.

A vexing problem in mitochondrial medicine is our limited capacity to evaluate the extent of brain disease in vivo . This limitation has hindered our understanding of the mechanisms that underlie the imaging phenotype in the brain of patients with mitochondrial diseases and our capacity to identify new biomarkers and therapeutic targets. Using comprehensive imaging, we analyzed the metabolic network that drives the brain structural and metabolic features of a mouse model of pyruvate dehydrogenase deficiency (PDHD). As the disease progressed in this animal, in vivo brain glucose uptake and glycolysis increased. Propionate served as a major anaplerotic substrate, predominantly metabolized by glial cells. A combination of propionate and a ketogenic diet extended lifespan, improved neuropathology, and ameliorated motor deficits in these animals. Together, intermediary metabolism is quite distinct in the PDHD brain-it plays a key role in the imaging phenotype, and it may uncover new treatments for this condition.

Neurons from layer II of the entorhinal cortex (ECII) are the first to accumulate tau protein aggregates and degenerate during prodromal Alzheimer's disease. Gaining insight into the molecular mechanisms underlying this vulnerability will help reveal genes and pathways at play during incipient stages of the disease. Here, we use a data-driven functional genomics approach to model ECII neurons in silico and identify the proto-oncogene DEK as a regulator of tau pathology.We show that epigenetic changes caused by Dek silencing alter activity-induced transcription, with major effects on neuronal excitability. This is accompanied by the gradual accumulation of tau in the somatodendritic compartment of mouse ECII neurons in vivo, reactivity of surrounding microglia, and microglia-mediated neuron loss. These features are all characteristic of early Alzheimer's disease.The existence of a cell-autonomous mechanism linking Alzheimer's disease pathogenic mechanisms in the precise neuron type where the disease starts provides unique evidence that synaptic homeostasis dysregulation is of central importance in the onset of tau pathology in Alzheimer's disease. By modelling neurons from the entorhinal cortex in silico, Rodriguez-Rodriguez et al. obtain evidence suggesting that the proto-oncogene DEK is likely to contribute to the vulnerability of these neurons to Alzheimer's disease. Reducing DEK levels in these neurons in vitro leads to changes reminiscent of early Alzheimer's disease pathology.

Dysregulated epigenetic states are a hallmark of cancer and often arise from genetic alterations in epigenetic regulators. This includes missense mutations in histones, which, together with associated DNA, form nucleosome core particles. However, the oncogenic mechanisms of most histone mutations are unknown. Here, we demonstrate that cancer-associated histone mutations at arginines in the histone H3 N-terminal tail disrupt repressive chromatin domains, alter gene regulation, and dysregulate differentiation. We find that histone H3R2C and R26C mutants reduce transcriptionally repressive H3K27me3. While H3K27me3 depletion in cells expressing these mutants is exclusively observed on the minor fraction of histone tails harboring the mutations, the same mutants recurrently disrupt broad H3K27me3 domains in the chromatin context, including near developmentally regulated promoters. H3K27me3 loss leads to de-repression of differentiation pathways, with concordant effects between H3R2 and H3R26 mutants despite different proximity to the PRC2 substrate, H3K27. Functionally, H3R26C-expressing mesenchymal progenitor cells and murine embryonic stem cell-derived teratomas demonstrate impaired differentiation. Collectively, these data show that cancer-associated H3 N-terminal arginine mutations reduce PRC2 activity and disrupt chromatin-dependent developmental functions, a cancer-relevant phenotype. Missense mutations in histones can drive oncogenesis and disrupt chromatin, but the associated mechanisms for many such mutations remain poorly understood. Here, the authors show that cancer-associated histone mutations at arginines in the H3 N-terminal tail disrupt repressive chromatin domains, alter gene expression, and in one case impair differentiation via reduction of PRC2 function.

The clonal raider ant, Ooceraea biroi , is a queenless species that reproduces asexually, and these traits make it an attractive model system for laboratory research. However, it is unclear where on the ant phylogeny these traits evolved, partly because few closely related species have been described and studied. Here, we describe a new raider ant species, Ooceraea hainingensis sp. nov. , from Zhejiang, China. This species is closely related to O. biroi but can be distinguished by the following features: 1) workers of O. hainingensis sp. nov. have an obvious promesonotal suture and a metanotal groove, whereas these characters are ambiguous in O. biroi ; and 2) the subpetiolar process of O. hainingensis is prominent and anteroventrally directed like a thumb with sublinear posteroventral margin, while in O. biroi , it is anteroventrally directed but slightly backward -bent. Molecular phylogenetic analyses confirm that O. hainingensis is genetically distinct from O. biroi . Importantly, unlike O. biroi , O. hainingensis has a queen caste with wings and well -developed eyes. This suggests that the loss of the queen caste and transition to asexual reproduction by workers is specific to O. biroi and occurred after that species diverged from closely related congeneric species.

Flaviviruses such as dengue virus (DENV), Zika virus (ZIKV), and yellow fever virus (YFV) are spread by mosquitoes and cause human disease and mortality in tropical areas. In contrast, Powassan virus (POWV), which causes severe neurologic illness, is a flavivirus transmitted by ticks in temperate regions of the Northern hemisphere. We find serologic neutralizing activity against POWV in individuals living in Mexico and Brazil. Monoclonal antibodies P002 and P003, which were derived from a resident of Mexico (where POWV is not reported), neutralize POWV lineage I by recognizing an epitope on the virus envelope domain III (EDIII) that is shared with a broad range of tick- and mosquito -borne flaviviruses. Our findings raise the possibility that POWV, or a flavivirus closely related to it, infects humans in the tropics.

Background Female Aedes aegypti mosquitoes can spread disease-causing pathogens when they bite humans to obtain blood nutrients required for egg production. Following a complete blood meal, host-seeking is suppressed until eggs are laid. Neuropeptide Y-like receptor 7 (NPYLR7) plays a role in endogenous host-seeking suppression and previous work identified small-molecule NPYLR7 agonists that inhibit host-seeking and blood-feeding when fed to mosquitoes at high micromolar doses. Methods Using structure-activity relationship analysis and structure-guided design we synthesized 128 compounds with similarity to known NPYLR7 agonists. Results Although in vitro potency (EC50) was not strictly predictive of in vivo effect, we identified three compounds that reduced blood-feeding from a live host when fed to mosquitoes at a dose of 1 mu M-a 100-fold improvement over the original reference compound. Conclusions Exogenous activation of NPYLR7 represents an innovative vector control strategy to block mosquito biting behavior and prevent mosquito-human host interactions that lead to pathogen transmission.